Fungus is a type of microorganism that causes fungal infection. A fungal infection is an inflammatory condition in which fungi multiply and invade the skin, the digestive tract, the genitals and other body tissues, particularly the lungs and liver. Fungal infections mainly include superficial and systemic fungal infections. Fungal infections are more common in people taking antibiotics, corticosteroids, immunosuppressant drugs and contraceptives. The fungal infections are prominent in people with endocrine disorders, immune diseases and other conditions such as obesity, AIDS, tuberculosis, major burns, leukemia and diabetes.
The current antifungal agents belong to various groups like polyenes, heterocyclic benzofuran, allylamines, antimetabolites, azoles, glucan synthesis inhibitors, etc. out of which azoles are presently the most extensively used antifungal agents. Azoles are further classified into imidazoles and triazoles. Fluconazole belongs to the family of triazole antifungals. Fluconazole is an important antifungal agent which is orally active and has low toxicity but its extensive use has resulted in emergence of fluconazole-resistant fungal strains. Therefore, it is necessary to meet the long-felt need to develop novel fluconazole analogues which exert high anti-fungal activity against various fungi. The presence of one triazole ring, halogenated phenyl ring and tertiary alcoholic oxygen functionality in azole class of compounds, is necessary for antifungal activity.
Various fluconazole analogues having antifungal activity have been reported in the literature. Some of the recent references describing synthesis and antifungal activity are given below:
Bioorganic & Medicinal Chemistry Letters 17 (2007) 3686-9; Bioorganic & Medicinal Chemistry Letters 18 (2008) 6538-6541; Bioorganic & Medicinal Chemistry Letters 19 (2009) 301-304; Bioorganic & Medicinal Chemistry Letters 19 (2009) 759-763; Bioorganic & Medicinal Chemistry Letters 19 (2009) 2013-2017; and Bioorganic & Medicinal Chemistry Letters 19 (2009) 3559-3563.
The racemic fluconazole analogues containing thieno-[2,3-d]pyrimidin-4(3H)-one moiety of Formula (2) and their excellent antifungal activities have already been described in our earlier patent publication, WO 2009109983, with the method of preparing such racemic compounds, which have high antifungal activity against various fungi.

Wherein, R1, R2, R3 and R4 are defined as above.
It has been found by the present inventors that one of the enantiomer of chiral fluconazole analogues containing thieno-[2,3-d]pyrimidin-4(3H)-one moiety has enhanced antifungal activity than corresponding racemic compounds. Hence, there is a need to develop such enantiomers which exert high antifungal activity against various fungal strains.
Accordingly, the present invention seeks to provide enantiomers of chiral fluconazole analogues of Formula (1a) and Formula (1b) containing thieno-[2,3-d]pyrimidin-4(3H)-one moiety and process thereof as an effort to come up with antifungal agents having broad spectrum of antifungal activity, for which the protection is sought.